A thinner cortex has higher potential for binding GABA receptor A which is associated with larger amplitudes of intrinsic brain activity (iBA). However, the relationship between cortical thickness and iBA is unknown in intact and epileptic brains. To this end, we investigated the relationship between cortical thickness measured by high-resolution MRI and surface-based iBA derived from resting-state functional MRI in normal controls (n = 82) and patients with generalized tonic-clonic seizures (GTCS) only (n = 82). We demonstrated that the spatial distribution of cortical thickness negatively correlated with surface-based iBA amplitude at both whole-brain and within independent brain functional networks. In GTCS patients, spatial coupling between thickness and iBA amplitude decreased in the default mode, dorsal attention, and somatomotor networks. In addition, the vertex-wise across-subject thickness-iBA amplitude correspondence altered in the frontal and temporal lobes as well as in the precuneus in GTCS patients. The relationship between these two modalities can serve as a brain-based marker for detecting epileptogenic changes.